POSSIBILITY OF NEW LYMPHATIC PATHWAY CREATION THROUGH NEO-LYMPHANGIOGENESIS INDUCED BY SUBDERMAL DISSECTION

Surgical intervention and subsequent wound healing process are known to induce neo-lymphangiogenesis, but few studies have been reported to utilize this mechanism for lymphedema treatment. The aim of this study was to evaluate feasibility of subdermal dissection for neo-lymphangiogenesis induction (SDN) to treat lower extremity lymphedema (LEL). Medical records of secondary LEL patients who had undergone ICG lymphography and SDN procedure were reviewed. SDN was performed by dissecting fat tissues just below the dermis from the most proximal area showing dermal backflow through abdominal-toaxillary lymphatic pathways. Perioperative lymphedematous conditions were evaluated with lymphedema quality of life score (LeQOLiS) and LEL index. Seventeen female patients were included. SDN could be performed in 10 minutes on average without postoperative complication. Postoperative ICG lymphography showed new lymphatic pathways in 6 (35.3%) cases. Postoperative LeQOLiS ranged from 9 to 66, which was statistically lower than preoperative LeQOLiS (32.9 ± 19.2 vs. 36.6 ± 19.3, p = 0.048), whereas there was no statistically significant difference between pre- and post-operative LEL index (275.2 ± 23.3 vs. 270.5 ± 20.8, P = 0.073). Subdermal dissection, although its probability is not high, has a potential to induce neo-lymphangiogenesis. Further studies are required to improve and demonstrate efficacy of the procedure for new lymphatic pathway creation.

Improved Bioavailability of Poorly Soluble Drugs through Gastrointestinal Muco-Adhesion of Lipid Nanoparticles

Gastrointestinal absorption remains indispensable in the systemic delivery of most drugs, even though it presents several challenges that, paradoxically, may also provide opportunities that can be exploited to achieve maximal bioavailability. Drug delivery systems made from nanoparticle carriers and especially, lipid carriers, have the potential to traverse gastrointestinal barriers and deploy in the lymphatic pathway, which aptly, is free from first pass via the liver. Several poorly soluble drugs have presented improved systemic bioavailability when couriered in lipid nanoparticle carriers. In this review, we propose an additional frontier to enhancing the bioavailability of poorly soluble drugs when encapsulated in lipid nano-carriers by imparting muco-adhesion to the particles through application of appropriate polymeric coating to the lipid carrier. The combined effect of gastrointestinal muco-adhesion followed by lymphatic absorption is a promising approach to improving systemic bioavailability of poorly soluble drugs following oral administration. Evidence to the potential of this approach is backed-up by recent studies within the review.

Novel bioemulsomes for baicalin oral lymphatic targeting: development, optimization and pharmacokinetics

Aim: The aim of this study was to elaborate on ‘bioemulsomes,' novel biocompatible lipoprotein analogs for effective lymphatic transport of baicalin (BCL). Methods: BCL bioemulsomes were developed and optimized and in vitro physicochemical characterization performed. The bioavailability of BCL bioemulsomes compared with free BCL was investigated using in vivo pharmacokinetics studies. Finally, BCL lymphatic transport was assessed via cycloheximide blockade assay. Results: Optimized BCL-loaded nanoemulsomes showed promising in vitro characteristics that favor lymphatic targeting. In vivo pharmacokinetics showed a significant improvement in bioavailability over free BCL. A significant decrease in BCL emulsome absorption (33%) was exhibited after chemical blockage of the lymphatic pathway, confirming the lymphatic transport potential. Conclusion: Bioemulsomes could be a promising tool for bypassing BCL oral delivery hurdles as well as lymphatic transport, paving the way for potential treatment of lymphoma.

Peri-operative imaging techniques of the sentinel lymph node in veterinary oncology

When cancer cells spread through lymphatic vessels, the first lymph node they reach is the sentinel lymph node (SLN). Hence, if the SLN is free from metastatic cells, it can be assumed that further lymph nodes will be free of metastatic tumor cells too. If metastatic tumor cells are identified in the SLN, the patient is at risk of developing distant metastatic disease. In that case, further diagnostic and therapeutic steps are needed and the patient’s prognosis gets worse. The SLN can be located at an anatomically unpredictable location. This is likely due to lymphangiogenesis, which alters the normal lymphatic pathway and drains the metastatic cells to another lymph node than the expected anatomically closest one. Therefore, identifying the SLN by an accurate mapping technique is necessary. In this article, the existing techniques for SLN mapping are reviewed, and their use in human and veterinary medicine is compared.

Lymphatic pathway evaluation in congenital heart disease using 3D whole-heart balanced steady state free precession and T2-weighted cardiovascular magnetic resonance

Background Due to passive blood flow in palliated single ventricle, central venous pressure increases chronically, ultimately impeding lymphatic drainage. Early visualization and treatment of these malformations is essential to reduce morbidity and mortality. Cardiovascular magnetic resonance (CMR) T2-weighted lymphangiography (T2w) is used for lymphatic assessment, but its low signal-to-noise ratio may result in incomplete visualization of thoracic duct pathway. 3D-balanced steady state free precession (3D-bSSFP) is commonly used to assess congenital cardiac disease anatomy. Here, we aimed to improve diagnostic imaging of thoracic duct pathway using 3D-bSSFP. Methods Patients underwent CMR during single ventricle or central lymphatic system assessment using T2w and 3D-bSSFP. T2w parameters included 3D-turbo spin echo (TSE), TE/TR = 600/2500 ms, resolution = 1 × 1 × 1.8 mm, respiratory triggering with bellows. 3D-bSSFP parameters included electrocardiogram triggering and diaphragm navigator, 1.6 mm isotropic resolution, TE/TR = 1.8/3.6 ms. Thoracic duct was identified independently in T2w and 3D-bSSFP images, tracked completely from cisterna chyli to its drainage site, and classified based on severity of lymphatic abnormalities. Results Forty-eight patients underwent CMR, 46 of whom were included in the study. Forty-five had congenital heart disease with single ventricle physiology. Median age at CMR was 4.3 year (range 0.9–35.1 year, IQR 2.4 year), and median weight was 14.4 kg (range, 7.9–112.9 kg, IQR 5.2 kg). Single ventricle with right dominant ventricle was noted in 31 patients. Thirty-eight patients (84%) were status post bidirectional Glenn and 7 (16%) were status post Fontan anastomosis. Thoracic duct visualization was achieved in 45 patients by T2w and 3D-bSSFP. Complete tracking to drainage site was attained in 11 patients (24%) by T2w vs 25 (54%) by 3D-bSSFP and in 28 (61%) by both. Classification of lymphatics was performed in 31 patients. Conclusion Thoracic duct pathway can be visualized by 3D-bSSFP combined with T2w lymphangiography. Cardiac triggering and respiratory navigation likely help retain lymphatic signal in the retrocardiac area by 3D-bSSFP. Visualizing lymphatic system leaks is challenging on 3D-bSSFP images alone, but 3D-bSSFP offers good visualization of duct anatomy and landmark structures to help plan interventions. Together, these sequences can define abnormal lymphatic pathway following single ventricle palliative surgery, thus guiding lymphatic interventional procedures.

Identification of intra-abdominal lymphatics in canine carcasses by laparoscopic fluorescence lymphography with intradermal and intrapopliteal ICG administration

Objective To evaluate the feasibility of laparoscopic fluorescence lymphography (LFL) using indocyanine green (ICG) via intradermal (ID) or intrapopliteal (IPP) administration in an ex vivo canine model. Methods Six thawed adult male dog carcasses were placed in the Trendelenburg position after placing three surgical ports in triangulation. ICG (0.5 mg/ml; 0.05 mg/kg) was administered to five of the carcasses (one carcass was a pilot) via ID in the left torso and IPP (right position, by surgical access) to stain the lymphatic pathway and medial iliac lymph node (MILN). Fluorescence quality, staining time, structures stained, and lymph node histopathology were assessed. Thoracic duct staining was also evaluated. Results ID administration showed staining of parts of the lymphatic pathway of the iliosacral lymph center in all cases using a single dose of ICG, with left MILN visualization in four carcasses. IPP administration showed staining of the right MILN in all cases, using a single dose in four carcasses. ICG reached the thoracic duct in one case. The two administration routes showed similar results in terms of required ICG volume, staining time, and visualization quality, although IPP was more effective in staining the MILN. Conclusions This study confirms the feasibility of staining the iliosacral lymph center (mainly the MILNs) by LFL in thawed dog carcasses via ID or IPP administration of ICG. However, the IPP route showed greater effectiveness in staining the MILN.